Mitogen-activated protein kinase kinase 5 regulates proliferation and biosynthetic processes in procyclic forms of Trypanosoma brucei

Kugeratski, F. G., Batista, M., Lima, C. V. d. P., Neilson, L. J., da Cunha, E. S., de Godoy, L. M., Zanivan, S., Krieger, M. A. and Marchini, F. K. (2018) Mitogen-activated protein kinase kinase 5 regulates proliferation and biosynthetic processes in procyclic forms of Trypanosoma brucei. Journal of Proteome Research, 17(1), pp. 108-118. (doi: 10.1021/acs.jproteome.7b00415) (PMID:29043805)

Abstract

The pathogenic protozoan T. brucei alternates into distinct developmental stages in the mammalian and insect hosts. The mitogen-activated protein kinase (MAPK) signaling pathways transduce extracellular stimuli into a range of cellular responses, which ultimately lead to the adaptation to the external environment. Here, we combined a loss of function approach with stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry (MS) to investigate the role of the mitogen-activated protein kinase kinase 5 (MKK5) in T. brucei. The silencing of MKK5 significantly decreased the proliferation of procyclic forms of T. brucei. To shed light on the molecular alterations associated with this phenotype, we measured the total proteome and phosphoproteome of cells silenced for MKK5. In the total proteome, we observed a general decrease in proteins related to ribosome and translation as well as down-regulation of several components of the fatty acids biosynthesis pathway. In addition, we observed alterations in the protein levels and phosphorylation of key metabolic enzymes, which point toward a suppression of the oxidative metabolism. Taken together, our findings show that the silencing of MKK5 alters cell growth, energy metabolism, protein and fatty acids biosynthesis in procyclic T. brucei.

• Item Type: Articles
• Keywords: Biochemistry, general chemistry.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kugeratski, Fernanda Grande and Neilson, Ms Lisa and Zanivan, Professor Sara
• Authors: Kugeratski, F. G., Batista, M., Lima, C. V. d. P., Neilson, L. J., da Cunha, E. S., de Godoy, L. M., Zanivan, S., Krieger, M. A., and Marchini, F. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Proteome Research
• Publisher: American Chemical Society (ACS)
• ISSN: 1535-3893
• ISSN (Online): 1535-3907
• Published Online: 18 October 2017
• Copyright Holders: Copyright © 2017 American Chemical Society
• First Published: First published in Journal of Proteome Research 17(1):108-118
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher